We are requesting funds for a Jeol DART accuTOF mass spectrometer system including a Gerstel MPS2 robotic autosampler with a cold injection system for GC separations. NIH funded investigators pursue metabolomic analyses in order to phenotype the metabolic consequences of genetic or disease alterations in humans and animal models. This research is compromised in Davis by the lack of instrumentation combining gas chromatographic separations with high mass accuracy and good sensitivity and isotope accuracy. In the Metabolomics Facility at UC Davis, over 22,000 low- resolution GC-TOF MS chromatograms have been screened for over 1,000 identified metabolites. Data were processed and stored in the unique BinBase database for comparison of peaks (including unknown compounds) across the 345 studies that were conducted so far. For the projects of the major users, these studies have yielded important data which led to a wide range of publications. We also found many compounds that were statistically significant in comparisons of case/control studies for which we need a good annotation scheme to perform biochemical assessments. The starting point for such annotations is to obtain accurate mass data for the molecular ions. We have compared our published results from soft ionization using chemical ionization in the (loaned) Waters GCTpremier to the alternative Jeol accuTOF mass spectrometer in conjunction with gas chromatography separation and DART ionization. Mass accuracy was acceptable with average mass errors of [unreadable]3 mu, but isotope accuracy was even better in the Jeol instrument than determined by the GCTpremier MS. We are therefore convinced that the Jeol GC-DART accuTOF mass spectrometer will have a major impact on the major users of this grant and the greater UC Davis research community. The instrument will be placed in the Metabolomics Facility core unit of the UC Davis Genome Center, with dedicated and trained staff available to oversee the operation, maintenance and management of this instrument. The Metabolomics Facility has been established in 2005 to provide cutting-edge research and service in collaboration with campus faculty, specifically to advance analytical and informatics methods to study metabolic dysregulation involving small molecules. The interaction between service core unit and research unit and the integration of these laboratories to a single Facility enables a regular improvement of methods and tools used by all staff in the Facility. The UC Davis Genome Center Metabolomics Facility core unit provides these services to two campuses (Sacramento and Davis) which include over 800 biology faculty and more than 4,000 graduate students.